scientists reported in Nature that they
were able to regrow heart tissue in mice
by coaxing injected bone marrow stem
cells into taking on a new identity as
heart cells.

“The net result was that a new field
was born,” says Hare, from Miami.
“Within a year there were papers where
people had tried this in humans.” Today,
hundreds of trials giving bone marrow
cells to heart patients are either ongoing or already completed. Some provide
stem cells shortly after a heart attack
to spare heavy damage; some involve
patients already in heart failure.

“The totality of evidence from the
clinical trials is positive,” says Hare, who
is conducting some of the trials and is on
the board of Stem Cell Therapeutics, a
Canadian-based company. “The heart is
pumping more blood per beat.” In March
in the journal Circulation Research, his
team described a study of eight patients
who received injections of bone marrow
cells near an area of the heart scarred due
to heart attack. After three months, the
patients’ heart contractions were stronger. Even more important, their hearts
later appeared to undergo some degree
of “reverse remodeling,” or an attempt
to return to normal anatomy, though the
precise mechanism isn’t known.

Problem is, no one knows whether
these kinds of improvements make any
difference for a patient’s survival. “The
definition of working means, ‘Do people
live longer and feel better?’ That study
has just been funded in Europe,” Hare
says. A team of investigators coordinated
by the European Society of Cardiology is
aiming to recruit 3,000 volunteers, half
of whom will receive bone marrow stem
cell injections after a heart attack and
half of whom will get a placebo. It will
be one of the largest studies so far using
stem cells to try to help heart patients,
and will go on long enough to detect any
survival advantage.

Heart of the matter
Cardiologists don’t agree about whether
this clinical trial and others are a good
idea. They also have concerns about the
inconsistency of many laboratory studies.

A study in 1-day-old mice reveals that the mammalian heart has early potential torenew. Images above show an injury on (from left) days two, seven and 21. Pumpingtissue takes the place of connective tissue (blue) that could lead to a stiff heart.

With full understanding of cardiac regeneration still lacking, some
researchers have cautioned against
launching headfirst into human experiments. “I think it’s been reassuring
and probably a little fortunate that we
haven’t hurt people,” says Lee. Among
the unanswered questions: Are the bone
marrow stem cells turning into heart
cells, or does the presence of bone marrow cells trigger some kind of dormant
mechanism in stem cells already residing in the heart? Could other tissues be
affected by the treatment?

“We don’t understand the mechanism
enough,” Lee says.

For instance, he says, lab studies
have suggested that the bone marrow
stem cells do not survive well, if at all,
once they are injected into the heart.
If true, it means that the bone marrow
cells are not becoming cardiac cells, but
that some other property accounts for
the study results. So patients might be
receiving an injection of bone marrow
cells that isn’t necessary.

A study published in September in
Science Translational Medicine raises the
possibility that a heart attack damages a
patient’s bone marrow cells, giving them
properties that make them less suited
for transplantation. Other populations
of stem cells might turn out to be more
efficient; some scientists are working to
create embryonic-like stem cells in the
lab that may be even more open to a new
identity than bone marrow stem cells.

“The closer we can get to understand-ing how these benefits occur,” Lee says,“the closer we can get to treatment.”The scientists conducting the trials,such as Hare, believe human studies arenecessary for progress, and can be donealongside vital basic research. “I wouldsay it’s been way too slow,” he says ofthe pace of clinical trials. About 5 mil-lion Americans currently experienceheart failure, left with options that willonly slow the decline of their health butnot offer a cure. He says he has no doubtthat a deeper scientific appreciation willemerge with five more years of investi-gation. Some patients can’t wait thatlong. “I see patients with permanentheart damage,” he says. “Half of themare going to die while we sort out ourscientific understanding.”Even if scientists learn how to prodthe growth of new heart cells, otherchallenges will remain. Growing muscleis not enough. The new tissue formingalongside the old still has to beat andcarry electrical signals in perfect syncwith neighboring cells. No one knowswhether that would happen, or how tomake it happen.

Explore more

s For more on heart development:
J. Epstein. “Cardiac development and
implications for heart disease.” New
England Journal of Medicine, 2010.